Ampicillin → Penicillanic Acid

Participants

Reaction Steps

The pyrazolinone acid obtained in (b) (0.10 g, 0.46 mmol) in dry dichloromethane (5 ml) was treated with triethylamine (0.10 ml, 0.7 mmol) and the solution cooled to -20° and treated with thionyl chloride(0.040 ml, 0.56 mmol) in dichloromethane (0.5 ml). The solution was then stirred 30 min. at -10°. Anhydrous ampicillin (0.15 g., 0.43 mmol) in dichloromethane (5 ml) was meanwhile separately treated with triethylamine (0.07 ml, 0.5 mmol); the suspension was stirred 20 mins. when further triethylamine (0.06 ml) was added to give a solution. This was cooled to 0° and the above pyrazolinone solution added dropwise. The whole was stirred 90 mins. at room temperature; 1 drop of 5 N HCl was added, the solution concentrated to low volume, ethyl acetate and water were added and the pH of the aqueous layer adjusted to 7.5 with sodium bicarbonate solution. The aqueous layer was separated, acidified to pH 1.5 (5 N HCl) and extracted with ethyl acetate. Drying (Na2SO4) and evaporation of the organic layer gave a crude product which was triturated with ethyl acetate (0.5 ml) to leave the desired title product as the solid free penicillanic acid (10 mg.) δ ((CD3)2CO+D2O) 1.49, 1.55 (2×3H, 2s, (CH3)2), 2.54 (3H, s, CH3 --C=), 4.29 (1H, s, C3 -penicillanic proton), 5.56 (2H, m, C5 and C6 -penicillanic protons), 5.89 (1H, s, --CH--CON--), 7.58 (11 H, complex, aryl and ring NH protons), 8.14 (partially exchanged --C--NH--CO). The free acid was converted to the sodium salt by suspension in water, addition of dilute sodium bicarbonate solution until, on shaking, dissolution occurred at pH 6.5, and freeze-drying.

Provenance & Evidence